1. Field of the Invention
The present invention relates to novel arylcycloalkyl derivatives, their production, and their use.
2. Description of Related Art
The chalcones of the following general formula Ia are known by the following prior art: ##STR2## 1. J.P. 281022--Compounds of formula Ia, wherein R.sub.1 =substituted phenyl,
R.sub.2 =OH, PA2 a=single or double bond, PA2 R.sub.3 =OH, PA2 R.sub.4a =H, isoprenyl or isopentyl, PA2 and are effective in treatment of diseases caused by hypersecretion of androgens, e.g., prostatomegaly, alopecia in males, acne vulgaris or seborrhoea. PA2 R.sub.1 =substituted phenyl, PA2 R.sub.2 =H, OH, acetoxy, carboxymethoxy or methoxycarbonylmethoxy, PA2 R.sub.3 =OH, methoxy, benzyloxy, H, PA2 R.sub.4a =H, isoprenyl or isopentyl, PA2 and possess anti-hyaluronidase activity. PA2 R.sub.1 =substituted phenyl, PA2 R.sub.2 =OH, acetoxy, carboxymethoxy, methoxycarboxylmethoxy, PA2 R.sub.3 =OH, methoxy, H, PA2 a=single or a double bond, PA2 R.sub.4a =isoprenyl, isopentyl, n-propyl or H, PA2 and are useful as aldose reductase inhibitors--used to treat diabetic complications such as cataracts, retinitis, nerve disorder or kidney disease. PA2 R.sub.1 =substituted phenyl, PA2 R.sub.2 =OH, PA2 R.sub.3 =OH, PA2 a=a double bond, PA2 R.sub.4a =H, PA2 and are useful as aldose reductase inhibitors--for treatment of diabetes mellitus complications. PA2 R.sub.1 =substituted phenyl, PA2 R.sub.2 =H or OH, PA2 R.sub.3 =H or OH, PA2 a=a double bond, PA2 R.sub.4a =H or OH, PA2 and are useful as c-kinase inhibitors and antitumor agents. PA2 R.sub.1 =substituted phenyl, PA2 R.sub.2 =H, halogen, lower alkyl, lower alkoxy, CN, carboxy, nitro, PA2 R.sub.3 =H, halogen, lower alkyl, lower alkoxy, CN, carboxy, nitro, hydroxy, substituted acetic acid derivative, PA2 a=a double bond, PA2 R.sub.4a =as in R.sub.3, PA2 and having inhibitory effect on hydroxy-prostaglandin dehydrogenase. They may have potential local activity against gastrointestinal disorders such as gastric ulcer, and ulcerative colitis. Other potential fields of application include the treatment of rheumatoid arthritis, circulatory disorders, cancer, lack of fertility and cell regulation. PA2 R.sub.1 =substituted phenyl, PA2 R.sub.2 =H, PA2 R.sub.3 =OH, PA2 a=a single bond, PA2 R.sub.4a =OH, PA2 and are selective inhibitors of 5-lipoxygenase and have excellent anti-allergic activity, thus are useful as a safe anti-allergic drug such as antiasthmatic, antiphlogistic and immune activating drug.
2. J.P. 026775--Compounds of formula Ia wherein PA1 3. J.P. 142166--Compounds of formula Ia wherein PA1 4. J.P. 248389--Compounds of formula Ia wherein PA1 5. J.P. 144717--Compounds of formula Ia wherein PA1 6. EP 150166--Compounds of formula Ia wherein PA1 7. J.P. 167288--Compounds of formula Ia wherein PA1 R.sub.3 is one, two, or three of the residues which are independent of each other and are selected from the group consisting of H, C.sub.1 -C.sub.6 -alkyl, --C(O)--C.sub.1 -C.sub.6 -alkyl, --C(O)--O--C.sub.1 -C.sub.6 -alkyl, OH, O--C.sub.1 -C.sub.6 -alkyl, --O--C(O)--C.sub.1 -C.sub.6 -alkyl, halogen; PA1 R.sub.4 is H, --OH, --O--C.sub.1 -C.sub.6 -alkyl, --O--C(O)--C.sub.1 -C.sub.6 -alkyl, --C(O)--OH, --C(O)--O--C.sub.1 -C.sub.6 -alkyl, O--C(O)--(C.sub.1 -C.sub.4 -alkyl-NH.sub.2, O--C(O)--(C.sub.1 -C.sub.4 -alkyl)-NH--(C.sub.1 -C.sub.4 -alkyl), O--C(O)--(C.sub.1 -C.sub.4 -alkyl)-N--(C.sub.1 -C.sub.4 -alkyl).sub.2 ; PA1 n 0, 1 or 2; and PA1 a represents an optional additional single bond, PA1 and to the physiologically tolerable salts thereof. PA1 a stands for an optional additional bond, PA1 and the physiologically tolerable salts thereof. PA1 R.sub.5 denotes one or two halogens or one or two C.sub.1 -C.sub.6 -alkyl or C.sub.1 -C.sub.3 -alkoxy groups, and a denotes an optional additional single bond, and the physiologically tolerable salts thereof. PA1 B) to get a compound of formula VI, a compound of formula V is treated with a peracid and the epoxide thus produced is treated with a hydride reagent or PA1 C) the compound of formula VI is produced by condensation of a suitable arene with cyclohexene oxide in the presence of an acid catalyst and PA1 D) a compound of formula VI is treated with acetic anhydride and a mineral acid to give a compound of formula VII, ##STR12## wherein R.sub.2 is methyl and R.sub.4 is O--C(O)--Me and E) a compound of formula VII as described under D) is demethylated by treatment with a Lewis acid or a demethylating agent to give a compound of formula VII wherein R.sub.2 denotes H and R.sub.4 denotes OC(O)Me and PA1 F) a compound of formula VII wherein R.sub.2 denotes H and R.sub.4 denotes OH is produced by treatment of a compound produced under E) with dilute alkali, and PA1 G) the compound of formula VII is converted into a compound of formula I (a=additional bond) by treatment with an appropriate aldehyde in the presence of a base and the compound of formula I (a=no additional bond) is produced by hydrogenation of the compound of formula I (a=additional bond), R.sub.1, R.sub.2 and R.sub.3, where not explained explicitly, having the meaning as indicated above. PA1 H) a compound of the formula II wherein R.sub.4 is an amino acid ester can be prepared by treating a compound of the formula II (wherein R.sub.4 is --OH) with an appropriate N-protected amino acid in the presence of dicyclohexyl carbodiimide and a weak base, for example, 2,4-dimethyl amino pyridine. The ester obtained can be subjected to deprotection of the amino function using a weak acid. The weak acid can be formic acid in the presence of anisaldehyde. The formate salt can be exchanged with the hydrochloride salt.